Research Network for Metals in Medicine

 

 

Professor Des R. Richardson

BSc., MSc., PhD., DSc. (UWA)

Position: Professor, University of New South Wales, Faculty of Medicine; Head of the Iron Metabolism and Chelation Program, Children’s Cancer Institute

Affiliation: University of New South Wales Faculty of Medicine, Children's Cancer Institute

Postal Address:
PO Box 81
Randwick NSW 2031
AUSTRALIA

Email: drichardson@ccia.org.au
Webpage: www.ccia.org.au


Research Profile

Professor Richardson is a well established independent investigator and NHMRC Principal Research Fellow and his entire career has been devoted to the field of iron metabolism and iron chelation. Indeed, he an international reputation in this field, and in 2001 he submitted and was subsequently awarded his D.Sc degree based upon this work. He is a relatively young scientist (40 years old) and has published in excess of 120 articles.

Dr. Richardson heads a dynamic research team consisting of 17 individuals including 8 experienced post-doctoral fellows. Moreover he has extensive experience in managing research projects and staff. His laboratory is highly productive and over the last 6 years has produced 77 publications in this area (41 in the last 2 years). On 75 of these papers, Dr. Richardson is either first or senior author, and 67 of these have only 1-3 authors, demonstrating these are primary investigations from his lab. Hence, his publication record represents a personal contribution rather than one built from extensive collaboration. These articles are published in a wide variety of high quality journals including Cell, EMBO J., JBC, Blood, Lancet, Cancer Res., Clin. Cancer Res., Mol. Pharmacol., J. Biol. Inorg. Chem, Biochemistry etc.

Prof. Richardson has held prestigious awards throughout his training including an NHMRC Ph.D Scholarship, MRC of Canada Post-Doctoral Fellowship and MRC of Canada Scholarship. This latter award is 5 year career award for new Assistant Professor’s similar to the NHMRC Fellowship award. He is invited regularly to write Chapters and also Editorials, Commentaries and Reviews for a variety of Prestigious International Journals (including Cell and Lancet). He is Molecules in Focus Editor of the International Journal of Biochemistry and Cell Biology (Impact Factor = 3.3) and is on the Editorial Board of Redox Report, J. Lab. Clin. Med. and BioMetals.

Dr.Richardson is frequently invited to examine national and international granting agencies, including the NIH. He has considerable experience in the commercial development of scientific advances and holds 4 patents. The investigators have access to exceptional facilities at the Children’s Cancer Institute Australia including their own purpose-built lab. Prof. Richardson is regularly invited to speak at national and international meetings, and has been actively involved in the organization of national and international conferences. He is currently Treasurer of the Society of Free Radical Research Australasia.

The Iron Metabolism and Chelation Program is involved in understanding the metabolic and molecular pathways involved in the trafficking of iron in normal and cancer cells. This includes the development of iron chelators for the treatment of a variety of diseases including iron overload, Friedreich’s ataxia and cancer.

Research from Prof. Richardson’s laboratory has resulted in the development of iron chelators for the treatment of all the diseases listed above and these compounds have been patented and their development is being supported by commercial grants. More recent work has begun to investigate the effect of metal complexes on the growth of tumor cells.

We have also have been successful in elucidating intracellular pathways of iron trafficking in cells and in understanding the function of proteins involved in binding iron.

A wide variety of techniques is used in Prof. Richardson’s lab, including synthesis of ligands, metal complexes and their characterisation using standard analytical techniques including X-ray crystallography (in collaboration with Assoc. Prof. Paul Bernhardt). The compounds synthesised are then assessed by a wide variety of in techniques that utilise skills from cellular biology, molecular biology and classical biochemistry. The studies extend to in vivo models including the generation of knockout mice to assess the biological function of Fe-binding molecules.



Selected Publications


2002-2004 from over 120

  1. Becker, E., Greer, J., Ponka, P. and Richardson, D.R. (2002) Erythroid differentiation and protoporphyrin IX down-regulate frataxin expression in Friend cells: Characterisation of frataxin expression compared to molecules involved in iron metabolism and hemoglobinisation. Blood 99:3813-3822.
  2. Lovejoy, D.B. and Richardson, D.R. (2002) Novel “hybrid” iron chelators derived from aroylhydrazones and thiosemicarbazones demonstrate high anti-proliferative activity that is selective for tumor cells. Blood 100:666-676.
  3. Kwok, J. and Richardson, D.R. (2002) Unexpected effects of doxorubicin on iron regulatory protein-RNA-binding activity: The iron and copper complexes of anthracyclines decrease RNA-binding activity. Mol. Pharmacol. 62: 889-901
  4. Chaston, T., Lovejoy, D., Watts, R.N., Richardson, D.R. (2003) Examination of the Anti-Proliferative Activity of Iron Chelators: Multiple Cellular Targets and the Different Mechanism of Action of Triapine compared to Desferrioxamine and the Potent PIH Analogue 311. Clin. Cancer Res. 9(1), 402-414.
  5. Watts, R.N., Ponka, P. and Richardson, D.R. (2003) Effects of nitrogen monoxide and carbon monoxide on molecular and cellular iron metabolism: Mirror-image effector molecules that target iron. Biochem. J. 369, 429-440.
  6. Lovejoy, D. and Richardson, D.R. (2003) Iron chelators as anti-neoplastic agents: Current developments and promise of the PIH class of chelators. Curr. Med. Chem. 10, 1065-1078.
  7. Kwok, J.C. and Richardson, D.R. (2003) Anthracyclines induce accumulation of ferritin iron in normal and neoplastic cells: Inhibition of the ferritin Fe mobilization pathway. Mol. Pharmacol. 63:849-861.
  8. Le, N.T.V. and Richardson, D.R. (2003) Potent iron chelators increase the mRNA levels of the universal cyclin-dependent kinase inhibitor, p21WAF1/CIP1, but paradoxically inhibit translation: A potential mechanism of cell cycle dysregulation. Carcinogenesis 24:1045-1058.
  9. Bernhardt, P.V., Caldwell, L.M., Chaston, T.B., Chin, P. and Richardson, D.R. (2003) Cytotoxic iron chelators: characterization of the structure, solution chemistry and redox activity of ligands and iron complexes of the di-2-pyridyl ketone isonicotinoyl hydrazone (HPKIH) analogues. J Biol Inorg Chem. 8(8):866-80
  10. Kwok, J.C. and Richardson, D.R. (2004) Examination of the mechanism(s) involved in doxorubicin-mediated iron accumulation in ferritin: Studies using metabolic inhibitors, protein synthesis inhibitors and lysosomotropic agents. Mol. Pharmacol. 64(1):(January issue, in press).
  11. Richardson, D.R. (2004) Mysteries of the transferrin-transferrin receptor interaction uncovered: Further Clues to Understanding Iron Uptake. Cell (February Issue; In Press).


Facilities

The Children’s Cancer Institute Australia supplies state-of-the-art facilities to perform our investigations. These new laboratories are purpose built for Prof. Richardson’s studies and have also been fully equipped. This infrastructure includes a cell culture facility, animal holding lab, dark room, centrifuges, gamma-counter, computers and basic equipment for molecular and cellular biology (eg., electrophoresis equipment, -80oC freezer, shaking incubators for bacterial growth, hybridisation ovens etc).


International Linkages

Professor Ted Baker – University of Auckland, New Zealand (Examination of the X-ray crystal structure of the Fe-binding protein transferrin)

Professors Victor Gordeuk and Mark Loyevsky -Howard University, Washington DC, USA (Development of Fe chelators for the treatment of malaria)

Professor Christopher Chitambar- Medical College of Wisconsin, Milwaukee, USA (Development of Gallium Complexes for the Treatment of Cancer).

Professor Ulf Brunk – Linkoping University, Sweden (Understanding the role of lysosomes in iron metabolism)